Biomedical subjects

Zhong Wang

Publications and source records attributed to Zhong Wang.

At least 37 records · Page 2Linked to original sources

PubMed2006

Randomized study of single instillation of epirubicin for superficial bladder carcinoma: long-term clinical outcomes.

PURPOSE: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for nonmuscle-invasive bladder cancer postoperation. We evaluated the long-term efficacy of single dose intravesical epirubicin for superficial bladder carcinoma recurrence. METHODS: Between June 1997 and May 1998, a total of 47 patients with resectable superficial bladder carcinoma (Ta-1, Grade 1-2), primary or recurrent with no recurrence during last one year, were enrolled in this study. All patients were randomized into 3 study groups: Group A-single epirubicin (80 mg/40 mL of normal saline) was administered into the bladder within 6 hours postoperation; Group B-40 mg Epirubicin consecutively; Group C-40 mg mitomycin C, consecutively. In Group B and C, instillation were given every week for 6- 8 weeks and then every one month for 10 months. Patients were followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months of treatment. The analyzed background factors were the therapeutic method, tumor recurrence, and side effects. RESULTS: Of the 47 patients, 43 (91.5 percent) were eligible and were followed up for 5 years postoperation. The disease free intervals of the three groups were found to have no significant differences (F = 10.28, p > 0.05). The recurrence rates were 35.7 percent (5/14), 33.3 percent (5/15), and 40 percent (6/15), respectively (chi(2)= 0.83, p > 0.05). Side effects of group A (13.6 percent) was lower than that of Group B or C (53.3 percent and 46.7 percent, respectively) significantly (chi(2) test, p < 0.01). CONCLUSIONS: These data indicate that single dose of epirubicin instillation postoperation can reduce the recurrence of superficial bladder carcinoma and has low side effects.

Administration, Intravesical↗

PubMed2006

Tumor localization and antitumor efficacy of novel sapphyrin compounds.

Sapphyrins are pentapyrrolic metal-free expanded porphyrins with potential medical use as anticancer agents. The novel sapphyrin derivative, PCI-2050, functionalized with 2-[2-(2-methoxyethoxy)ethoxy]ethoxy groups to enhance solubility and a modified bipyrrole moiety was found to be more potent in inducing apoptosis than the previously described sapphyrin PCI-2000. Because some sapphyrins may localize to tumors, we took advantage of the intrinsic fluorescence of these compounds to develop a flow cytometry-based assay to track sapphyrin biodistribution in tumor-bearing mice. Ex vivo analysis of sapphyrin-injected animals revealed that PCI-2050 preferentially localized to tumor, whereas PCI-2000 distributed into normal tissues rather than tumor. PCI-2050 uptake in xenograft tumor cells and resultant tumor cell cytotoxicity was dose dependent. To investigate structure-activity relationships, we focused on PCI-2050 and three derivatives that differ by their alkyl substituents on the bipyrrole moiety: PCI-2051, PCI-2052, and PCI-2053. Treatment of Ramos cells in culture or treatment of Ramos xenograft-bearing animals with each of the sapphyrins followed by ex vivo growth of tumor cells revealed the same pattern of cytotoxicity: PCI-2050 > PCI-2052 > PCI-2051 > PCI-2053. Thus, subtle changes in the alkyl substituents on the bipyrrole moiety result in significant changes in antitumor activity. PCI-2050 displayed significant antitumor efficacy in both Ramos and RKO xenograft models without hematologic, hepatic, or renal abnormalities as assessed by complete blood counts and serum chemistries. On the basis of these findings, it is concluded that the sapphyrin PCI-2050 warrants further evaluation as a potential anticancer agent due to its intrinsic proapoptotic activity and tumor localization ability.

Animals↗

PubMed2006

Room temperature formation of ammonia by oxidizing hydrogenated cerium nanoparticles in the air.

Ammonia formation was observed when hydrogenated cerium nanoparticles prepared by hydrogen plasma-metal reaction (HPMR) were exposed to the air at room temperature. This novel phenomenon represents a successful example of room temperature cleavage of dinitrogen and may find application in low temperature synthesis of ammonia under thermodynamically favorable conditions. A possible mechanism is also proposed. We suggest that the oxidation of cerium hydride offers chemical force to drive the hydrogen atoms out of the lattice. The monoatomic H released to the surface is highly active and readily reacts with N2 to yield ammonia. Some surface processes, which we know little about at the moment, are likely to be involved so as to lower the energy barrier of nitrogen dissociation. Further investigation is required to elucidate the detailed mechanism.

Air↗

PubMed2006

Widespread and stable pancreatic gene transfer by adeno-associated virus vectors via different routes.

Diabetes is a disease of epidemic proportions and is on the rise worldwide. Gene therapy has been actively pursued but limited by technical hurdles and profound inefficiency of direct gene transfer to the pancreas in vivo. Here, we show that, for the first time, appropriate serotypes of adeno-associated virus (AAV), coupled with a double-stranded vector DNA cassette, enable extensive and long-term in vivo gene transfer in the adult mouse pancreas by three different delivery methods. Intraperitoneal and intravenous delivery of AAV8 effectively transduced exocrine acinar cells as well as endocrine beta-cells, while local pancreatic intraductal delivery of AAV6 showed the best efficiency in the beta-cells among all AAV serotypes tested in this study. Nearly the entire islet population showed gene transfer but with distinct gene transfer efficiency and patterns when different delivery methods and vectors were used. Importantly, localized gene delivery coupled with an insulin promoter allowed extensive yet specific gene expression in the beta-cells. These effective new methods should provide useful tools to study diabetes pathogenesis and gene therapy.

Actins↗

PubMed2006

[Changes in the activities of enzymes involved in starch synthesis and accumulation in caryopsis of transgenic rice with antisense Wx gene].

The amylose content of rice caryopsis is determined by Wx protein, one kind of granule-bound starch synthetase which is encoded by Wx gene. Different rice types and species have different levels of Wx gene expression and have different amylose contents in their caryopsis. Wuyunjing No.7 (2200), the japonica rice with an amylose content 17% and its transgenic rice lines with antisense Wx gene (2201 and 2203, with amylose contents 8.5% and 2% respectively), and Longtefu (LP03), the indica rice with a high amylose content (28%) and its transgenic rice with antisense Wx gene (A199, with an amylose content 9%) were used to investigate the effects of Wx protein content decrease on the activities of enzymes involved in starch synthesis and thereby starch accumulation. The results indicated that with the decrease in Wx protein, the amylose content in transgenic caryopsis was reduced accordingly, whereas the amylopectin content per caryopsis (mg/grain) was not affected, and made the total starch content in transgenic caryopsis markedly lower than their parents. With the development of caryopsis, the amylose/total starch ratio was not changed significantly in the two parent caryopses, LP03 and 2200, but it went down gradually in their transgenic caryopses. The amylose/total starch ratio in transgenic caryopses was very significantly lower than their parents in the same period. The activities of ADP-glucose pyrophosphorylase (ADPG-PPase), granule-bound starch synthase (GBSS), soluble starch synthase (SSS) and starch branching enzyme (SBE) rose rapidly in early periods of grain filling, and soon reached their maximum, then reduced quickly until the middle and later periods of grain filling. Compared with the parents, the GBSS activity in transgenic caryopsis was significantly lowered, and correlated with the amylose reduction. Besides, the maximum activity of GBSS appeared earlier, and the range of the activity was smaller. In transgenic caryopsis, the activities of ADPG-PPase and SSS were higher than their parents in early and middle periods of grain filling, while the SBE activity was higher than their parents in middle and late periods.

1,4-alpha-Glucan Branching Enzyme↗

PubMed2006

[Application of magnetic resonance DW imaging technique in studying treatment of cerebral ischemia in rats by single or combined use of jasminoidin and cholalic acid].

OBJECTIVE: To estimate the therapeutic effect of single or combined use of jasminoidin and cholalic acid on focal cerebral ischemia rat with magnetic resonance-diffusion-weighted imaging (MR-DWI) technique, ultra-microscopy, and neuro-behavior scoring. METHODS: The model of cerebral ischemia-reperfusion injury was induced by string method. Three hours after reperfusion, MR-DWI was applied with ultra-microscopy and neuro-behavior test to give evaluation on cerebral ischemic rats, and pathologic, ultramicroscopic observation of tissue were taken as adjuvant measures to comprehensively evaluate the pharmacological effect on ischemia-reperfusion rats and delimit the efficacy of the two different components and their combination. RESULTS: Compared with the model group, ADC and DCavg values of the foci in all the treated groups had the incrensing trend. There was significant difference arund the foci in the group of combined use of jasminoidin and cholalic acid (P < 0.05). CONCLUSION: Combined use of jasminoidin and cholalic acid had protective effects on nerve and brain. MR-DWI technique accompanied with ultramicroscopic observation of tissues and neuro-behavior test is an effective method for evaluating the effect of neuro-protective agent.

Animals↗

PubMed2006

[One case report of primary penile malignant lymphoma (with a review of 24 case reports)].

OBJECTIVE: To investigate the early diagnosis and early treatment of primary penile malignant lymphoma. METHODS: One case of rare primary penile malignant lymphoma was studied with regard to its primary clinical process and characteristics, differential diagnosis and therapeutic method. The application value of the immunohistochemical features, in clinical diagnosis was analyzed. RESULTS: Surgical treatment of removing the penis, testes and scrotum was carried out, followed by chemotherapy went. The immunohistochemical tests showed CD56, granzyme B, perforin and cytoplasmic CD3epsilon to be positive, and surface CD3 negative. CONCLUSION: Primary malignant lymphoma of the penis, though rare clinically, may be treated effectively if diagnosed early. Wedge biopsy with histological examination and immunohistochemical tests is the most common method for definite diagnosis.

Adolescent↗

PubMed2006

[Effect of some active Chinese herbal fraction on brain tissue proteomic profile of ischemic mouse].

OBJECTIVE: To study the effect of some active Chinese herbal fraction on protein expression of brain tissue in ischemic mouse with proteomic technique. METHODS: Ischemia-reperfusion mice were treated with baicalin, geniposide, cholic acid and concha margaritifera respectively for 3 hrs, and then their brain tissue were taken to extract the total protein. Protein expression in ischemic mouse brain was analyzed with surface-enhanced laser desorption/inionation-time of flight-mass spectra (SELDI-TOF-MS) protein-chip. RESULTS: The four components tested had effect on 3 target proteins at 5373Da, 5707Da and 15103Da, showing the nature of multi-target and with different action on protein expression. CONCLUSION: Protein-chip is an effective approach for exploring the pharmacological mechanism of Chinese herbal fraction.

Animals↗

PubMed2006

[Pharmacological evaluation of baicalin and jasminoidin and their combination on focal cerebral ischemia-reperfusion injury].

OBJECTIVE: To elucidate the therapeutic effect and the influence on PI3K-Akt-PKB-BAD-CREB-PCREB pathway in focal cerebral ischemia rat responses before and after treatment with baicalin and jasminoidin given alone or in combination. METHOD: Rat model of ischemia reperfusion was established with thread. Generally accepted methods were used, including TTC staining, behavior test, as well as micro and ultra microscopy which can dynamically and accurately monitor pathological and physiological changes after cerebral ischemia on earlier period, to evaluate the brain injury induced by ischemia and the attenuations by the drugs. The difference of PI3K-Akt-PKB-BAD-CREB-PCREB expression was detected by western-blot technology. RESULT AND CONCLUSION: The combination of baicalin and jasminoidin composition can be potential neuroprotective agent. TTC staining technology combined with behavior grade and ultrmicro-structure observation on brain tissue is effective method to evaluate protective agent, which is related to signal transduction PI3K-Akt-PKB-BAD-CREB-PCREB pathway. The results provide benofical basis for revealing the complex of therapeutic mechanism of traditional Chinese medicine Qingkai Ling (QKL).

Animals↗

PubMed2005

Sustained whole-body functional rescue in congestive heart failure and muscular dystrophy hamsters by systemic gene transfer.

BACKGROUND: The success of muscular dystrophy gene therapy requires widespread and stable gene delivery with minimal invasiveness. Here, we investigated the therapeutic effect of systemic delivery of adeno-associated virus (AAV) vectors carrying human delta-sarcoglycan (delta-SG) gene in TO-2 hamsters, a congestive heart failure and muscular dystrophy model with a delta-SG gene mutation. METHODS AND RESULTS: A single injection of double-stranded AAV serotype 8 vector carrying human delta-SG gene without the need of any physical or pharmaceutical interventions achieved nearly complete gene transfer and tissue-specific expression in the heart and skeletal muscles of the diseased hamsters. Broad and sustained (>12 months) restoration of the missing delta-SG gene in the TO-2 hamsters corrected muscle cell membrane leakiness throughout the body and normalized serum creatine kinase levels (a 50- to 100-fold drop). Histological examination revealed minimal or the absence of central nucleation, fibrosis, and calcification in the skeletal muscle and heart. Whole-body functional analysis such as treadmill running showed dramatic improvement, similar to the wild-type F1B hamsters. Furthermore, cardiac functional studies with echocardiography revealed significantly increased percent fractional shortening and decreased left ventricular end-diastolic and end-systolic dimensions in the treated TO-2 hamsters. The survival time of the animals was also dramatically extended. CONCLUSIONS: Systemic gene transfer of delta-SG by the AAV serotype 8 vector could effectively ameliorate cardiac and skeletal muscle pathology, profoundly improve cardiac and whole-body functions, and significantly prolong the lifespan of the treated TO-2 hamsters.

Animals↗

PubMed2005

Gadolinium texaphyrin-methotrexate conjugates. Towards improved cancer chemotherapeutic agents.

Conjugates between methotrexate (MTX, Matrex, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-l-glutamic acid), an antifolate cancer chemotherapeutic to which resistance is often observed, and motexafin gadolinium (MGd), an experimental agent demonstrating selective tumor localization, are described. These systems were prepared in order to test whether linking these two species would produce agents with enhanced activity relative to MTX alone. Both ester- and amide-linked conjugates were synthesized starting from MGd and MTX. The ester conjugate showed greater in vitro anti-proliferative activity against the A549 lung carcinoma cell line at short incubation times than did MTX alone. Neither the amide conjugate, nor MGd, showed any observable activity under these in vitro conditions. These results are rationalized in terms of enhanced cellular uptake of both the ester and amide conjugates that is coupled with an effective rate of release (e.g., inherent or enzyme-mediated hydrolysis) in the case of the ester-linked conjugate, but not the corresponding amide system.

Antineoplastic Agents↗

PubMed2005

A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.

During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world. A new coronavirus (SARS-CoV) was identified as the SARS pathogen, which triggered severe pneumonia and acute, often lethal, lung failure. Moreover, among infected individuals influenza such as the Spanish flu and the emergence of new respiratory disease viruses have caused high lethality resulting from acute lung failure. In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor. The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses.

Analysis of Variance↗

PubMed2005

Induction of tumor immunity and cytotoxic t lymphocyte responses using dendritic cells transduced by adenoviral vectors encoding HBsAg: comparison to protein immunization.

Dendritic cells (DC) are specialized antigen-presenting cells with powerful immunostimulatory properties. Their use for induction of anti-tumor immunity has been limited by several factors, including identification of appropriate tumor-associated antigens, delivery of antigens to DC, and maintaining DC in a highly activated state. Here, DC propagated in vitro were transduced with an adenoviral (Ad) vector to express hepatitis B surface antigen (HBsAg), an antigen present in hepatocellular carcinoma (HCC). Many patients with HCC demonstrate evidence of prior HBV exposure, suggesting that the presence of the virus in a quiescent state may promote tumorigenesis. Ad-HBsAg-transduced DC stimulated strong cytotoxic T lymphocyte (CTL) responses to HBsAg-expressing tumor cells, and protected mice from lethal tumor challenge. Immunity was antigen-specific, as wild-type tumor (HBsAg -) grew normally. Furthermore, DC transduced with an irrelevant vector had no effect. Vaccination with HBsAg protein, a clinically utilized preparation that confers immunity to HBV infection, did not protect against tumor challenge even though it induced a strong antibody response. These studies describe for the first time the contributions of humoral and cellular immune responses to tumor immunity induced by Ad-transduced DC compared to protein vaccination.

Adenoviridae↗

PubMed2005

Regulation of yeast glycogen phosphorylase by the cyclin-dependent protein kinase Pho85p.

Yeast accumulate glycogen in response to nutrient limitation. The key enzymes of glycogen synthesis and degradation, glycogen synthase, and phosphorylase, are regulated by reversible phosphorylation. Phosphorylation inactivates glycogen synthase but activates phosphorylase. The kinases and phosphatases that control glycogen synthase are well characterized whilst the enzymes modifying phosphorylase are poorly defined. Here, we show that the cyclin-dependent protein kinase, Pho85p, which we have previously found to regulate glycogen synthase also controls the phosphorylation state of phosphorylase.

Cyclin-Dependent Kinases↗

PubMed2005

Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart.

Systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. Previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventions to enforce broad vector distribution. We compared the efficiency of multiple adeno-associated virus (AAV) vectors after a single injection via intraperitoneal or intravenous routes without additional intervention. We show that AAV8 is the most efficient vector for crossing the blood vessel barrier to attain systemic gene transfer in both skeletal and cardiac muscles of mice and hamsters. Serotypes such as AAV1 and AAV6, which demonstrate robust infection in skeletal muscle cells, were less effective in crossing the blood vessel barrier. Gene expression persisted in muscle and heart, but diminished in tissues undergoing rapid cell division, such as neonatal liver. This technology should prove useful for muscle-directed systemic gene therapy.

Animals↗

PubMed2005

The division of Drosophila germline stem cells and their precursors requires a specific cyclin.

A fundamental yet essentially unexplored question in stem cell biology is whether the stem cell cycle has specific features. Three B-cyclins in Drosophila, Cyclins (Cyc) A, B, and B3, associate with CDK1 and play partially redundant roles in embryogenic mitosis . Here, we show that the division of Drosophila GSCs and their precursors, the primordial germ cells (PGCs), specifically requires CycB. CycB is ubiquitously expressed in both germline and somatic lineages. However, CycB mutation does not have obvious effect on somatic development but causes PGCs to severely under proliferate. Moreover, both female and male CycB mutant GSCs fail to be maintained properly. Removing Cyclin B specifically from female GSCs causes the same defect, confirming the direct and cell-autonomous function of Cyclin B for GSC division. In contrast, two other G2 cyclins, CycA and CycB3, are also expressed in PGCs and GSCs, but overexpressing CycA cannot rescue the CycB mutant defects. These results indicate that the requirement of CycB for PGC and GSC divisions unlikely reflects the insufficient level of G2 cyclins in the CycB mutant but is in favor of a distinct function of CycB in these cells. Our results indicate that stem cells may use specific cell cycle regulators for their division.

Animals↗

PubMed2005

Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation.

The transition from a Drosophila ovarian germline stem cell (GSC) to its differentiated daughter cell, the cystoblast, is controlled by both niche signals and intrinsic factors. piwi and pumilio (pum) are essential for GSC self-renewal, whereas bag-of-marbles (bam) is required for cystoblast differentiation. We demonstrate that Piwi and Bam proteins are expressed independently of each other in reciprocal patterns in GSCs and cystoblasts. However, overexpression of either one antagonizes the other in these cells. Furthermore, piwi;bam double mutants phenocopy the bam mutant. This epistasis reflects the niche signaling function of piwi because depleting piwi from niche cells in bam mutant ovaries also phenocopies bam mutants. Thus, bam is epistatic to niche Piwi, but not germline Piwi function. Despite this, bam- ovaries lacking germline Piwi contain approximately 4-fold fewer germ cells than bam- ovaries, consistent with the role of germline Piwi in promoting GSC mitosis by 4-fold. Finally, pum is epistatic to bam, indicating that niche Piwi does not regulate Bam-C through Pum. We propose that niche Piwi maintains GSCs by repressing bam expression in GSCs, which consequently prevents Bam from downregulating Pum/Nos function in repressing the translation of differentiation genes and germline Piwi function in promoting germ cell division.

Animals↗

PubMed2005

Identification of potential biomarkers of Peyronie's disease.

AIM: To identify proteins that are differentially expressed in cells derived from normal and diseased tunica albuginea (TA) as related to Peyronie's disease (PD). METHODS: Cells with characteristics of fibroblasts were isolated from two tissue sources. Those from the plaque of patients with PD were designated as PT cells, and those from the normally-appearing TA of the same patients were designated as NT cells. Messenger RNAs of these cells were analyzed by real-time polymerase chain reaction (RT-PCR) for the expression of monocyte chemoattractant protein 1 (MCP-1). Crude protein lysates were analyzed by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS) with IMAC30-Cu, CM10, and H50 chips. Each lysate was then separated into six fractions, which were further analyzed by SELDI-MS. RESULTS: RT- PCR analysis showed that PT cells expressed higher levels of MCP-1 than their counterpart NT cells. SELDI-MS analysis showed that the crude protein lysates of all four cell strains produced similar and reproducible protein profiles on IMAC30-Cu and CM10 chips. Additional SELDI-MS analyses with the fractionated lysates detected three proteins of 11.6 kDa, 14.5 kDa, 22.6 kDa that were upregulated in PT cells and two proteins of 6.3 kDa and 46.9 kDa that were downregulated in PT cells. CONCLUSION: MCP-1, which is often involved in tissue fibrosis, was expressed at higher levels in PT than that in NT cells. Five potential biomarkers for PD were identified by SELDI-MS analysis.

Base Sequence↗